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Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

ABSTRACT: In the last few years we have witnessed increasing availability of proton therapy in the United States and worldwide. As a result, proton therapy is considered as either a primary or adjunctive approach for numerous indications where conventional radiation therapy shows promise but is accompanied by toxicities. Age-related macular degeneration (AMD) remains the leading cause of adult blindness in industrialized nations, and third worldwide, following cataract and glaucoma. Current standard therapy is intravitreal injection of anti-vascular endothelial growth factor agents. While this treatment shows improvement and stabilization in visual acuity for 40% of patients, 60% still experience disease progression. These injections are costly, necessitate repeated office visits, and carry the risk of endophthalmitis. The pathophysiology underlying neovascular AMD (nAMD) underscores the need to simultaneously target multiple pathways to retain useful vision. Radiation can be antiangiogenic, anti-inflammatory, and antiproliferative. Early photon therapy clinical trials were heterogeneous, and a Cochrane review of data demonstrated usefulness in treatment of nAMD but recommended further studies. Advantages of proton therapy over photon therapy include the ability to deliver a focal dose to the target while minimizing dose to normal structures, which is enhanced by unique treatment planning software that uses fluorescein angiography to verify target location and allows conformation of dose to the irregular shape and thickness characteristic of choroidal neovascular membranes, the pathognomonic finding in nAMD. Preliminary data suggest a potential role for proton therapy in the treatment of nAMD. In this article we review previous treatments for AMD, including those with both photon and proton radiation, and recommend future directions for clinical investigations to evaluate the role of proton therapy as an adjunct to antiangiogenic therapy, the current standard of care in this challenging setting.

SUBMITTER: Rice SR

PROVIDER: S-EPMC6871634 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

Rice Stephanie R SR Katz Matthew S J MSJ Mehta Minesh P MP

International journal of particle therapy 20160324 4

In the last few years we have witnessed increasing availability of proton therapy in the United States and worldwide. As a result, proton therapy is considered as either a primary or adjunctive approach for numerous indications where conventional radiation therapy shows promise but is accompanied by toxicities. Age-related macular degeneration (AMD) remains the leading cause of adult blindness in industrialized nations, and third worldwide, following cataract and glaucoma. Current standard thera ...[more]

PMID: 31772967

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Project description:Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.

Dataset Information

Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

Publications

Context for Protons as Adjunctive Therapy in Neovascular Age-Related Macular Degeneration: A Review.

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